CHRONIC PHYSICAL-ACTIVITY ALTERS HEPATOBILIARY EXCRETORY FUNCTION IN RATS

Recent studies have indicated that exercise causes alterations in the biotransformation of some xenobiotics and the clearances of antipyrine and [C-14]aminopyrine. The present study has investigated whether chr onic voluntary physical activity alters hepatobiliary excretory functi on by comparing the clearance and biliary excretion of model substrate s for each of four carrier-mediated transport systems (anion, uncharge d, bile acid and cation; n = 8 for each chemical in each group) in act ive and inactive female rats. The active rats had access to running wh eels and voluntarily ran 11.2 +/- 0.68 km/day. The active rats were fe d ad libitum, and ate 37% more food than weight-matched, restricted-fe d sedentary control rats. Basal bile flow was 34% higher in active rat s than in inactive rats, and excretion of bile acids, cholesterol and phospholipid were also increased. The biliary excretion and biliary cl earance of the anion, indocyanine green, were elevated in active rats, although total clearance and serum concentrations were not different due to decreased non-biliary clearance. Serum elimination and total cl earance of the uncharged substrate, ouabain, were elevated in the acti ve rats, due entirely to increased nonbiliary clearance. Total clearan ce of the bile acid, taurocholate, was higher in active rats due to an increased biliary clearance. In contrast, there were no differences i n either the biliary excretion or clearances of the cation, procainami de ethobromide, between the two groups of rats. Finally, no difference s in volume of distribution or elimination half-life were noted betwee n inactive and active rats for any of the substrates. Thus, chronic vo luntary physical activity increases the excretion or clearance of cert ain substrates and could potentially alter the effects of therapeutic drugs.